Alterations in dopamine transmission occur during drug abuse and addiction. To understand these changes, it is necessary lo first understand the basic physiology that underlies dopamine transmission. The aim of this Pathway to Independence Award (K9WR(K)) proposal is to investigate the mechanisms of dopamine transmission while providing the candidate (Dr Christopher Ford) with the necessary mentored training in electrophysiological and electrochemical techniques. The applicant has completed the K99 mentored phase of the award and has secured an independent tenure tract Assistant Professor position in the Department of Physiology and Biophysics at the Case Western Reserve University School (f Medicine. Having completed 2 of the three aims of the original research proposal and having met his initial career goal of becoming an independent investigator studying the cellular and molecular basis of addiction, this current pha.se of the proposal (R(X)) is designed to provide independent support that will I K used to further his studies, complete the remaining aims of the award and gain long-lemi ROI grant support. The central aim of this proposal is to determine the relationship between extracellular dopamine and i(s physiological consequences. The objective during the mentored phase will be to determine the mechanisms regulating dopamine transmission. The hypothesis to be tested is that dopamine mediates transmission in the VTA in a tightly regulated, synaptic manner. The objective during the independent phase will be to define the concentration and duration of dopamine mediating transmission. The hypothesis being that transient, high concentrations of dopamine mediate transmission. A lack of knowledge of the basic mechanisms of dopamine transmission has hindered progress towards determining how transmission becomes dysregulated during the course of drug addiction. Thus this work has the potential to identify and direct new strategies to treat drug abuse and addiction.